Substituted alkylphenols and meth



Reissued Mar. 29, 1938 p Re,

SUBSTITUTED ALKYLPHENOLS AND METH- OD OF PRODUCING THE SAME Frederick F. Blicke,' Ann Arbor, Mich, assignor to Regents of the University of Michigan, Ann Arbor, Mich., a corporation of Michigan No Drawing. Original No. 1,980,966, dated November 13, 1934, Serial No. 659,024, February 28, 1933. Application for reissue October 7, 1936, Serial No. 104,564

12 Claims. (Cl. 260-454) My invention relates to substituted alkylphenols in the 2 position, or nuclear substituents in the and the method of producing the same. My in- 2,6 positions, or a mixture of such products. vention has to do, more particularly, with the Zincke, Schneider and Emmerich (Ann, 328, 277 production of 4-alkylphenols, having substituents (1903)) have heretofore described the production 5 replacing one or more of the hydrogen atoms. of 2-chloro-4-methy1phenol, but no germicidal 5 In general, it is the object of my invention to tests were conducted by them on this substance. provide new products having high phenol coef- Tests have shown that it possesses a relatively ficients, low toxicity and valuable therapeutic low phenol coefiicient and does not have marked properties, which products will have utility begermicidal powers.

cause of their antiseptic and germicidal proper- My research has shown that, in general, the 10 ties. phenol coefiicient increases with the number of In general, my invention relates to new subcarbon atoms in the alkyl group and that, where stitution products of 4-alkylphenols, containing the alkyl group has less than three carbon atoms, more than two carbon atoms in the alkyl group, the phenol coefiicient is low and the germicidal and which possess substituents, preferably nup e s Of t e p d t e 11011 markfldy 5 clear substituents, in the 2 or 2,6 positions. vention, therefore, is restricted to-substituted 4- It is known that 4-alkylphenols are potent alkylphenols containing more than two carbon germicides. It is also known that the introducatoms in the alkyl p. as these pp r to be tion of such nuclear substituents as chlorine or the product having marked germicidal P bromine, augment the germicidal action of a The alkyl r p y be f h straight or of the 20 phenol, but, heretofore, no 4-alkylphenol having branched Chain yp such nuclear substituents as chlorine or bromine, I believe that suhstitutifln, in the 2 D has been made, which had a marked germicidal tions in the y ph 01 n in n more han effect. My invention relates to the preparation two carbon atoms in the alkyl p. of y of new products having in general a formula ex- Clea! substituent, 0f the gTOuP including t a 25 pressed as follows: ogens, CN, N02, and HgOH, will result in an in- 0H crease in the phenol coefiicient and yield prod- 1 X ucts having marked germicidal powers, but, at 6 2 this time, I have not yet investigated the germi- 5 3 cidal powers of any of these substitution prod- 3O ucts other than those in which the nuclear substituent is chlorine. in which the substituent indicated by X may The following specific example illustrates one be any one of the group including the halogens, method by means of which I have obtained 2- CN, N02, and HgOH, and the alkyl radical, inchloro-4-n-heptylphenol: 48 g. of 4-n-hepty1- 35 dicated by R and having the general formula phenol are mixed with 34 g. of sulfuryl chloride- CnH2n+1, may be any of these alkyl radicals in and after five days the material is distilled diwhich n is greater than 2. In other Words, I rectly or it may first be washed free from, halogen propose to prepare 4-alkylphenols in which the compounds with sodium bicarbonate solution and 40 alkyl group contains more than two carbon atoms the chlorophenol purified by distillation. The 40 and has a nuclear substituent, in the 2 position, pr c 2- h r0-4 -h p y h 01 is rily of the group above indicated. obtained as a liquid which is practically colorless,

In many cases the formation of such a product odorless and tasteless and which boils at will take place simultaneously with the formation under about 733 pressure- The of a similar product, in which the substituents solid alpha naphthoate produced from this com- 45 will be in the 2,6 positions, as indicated by the pound melts at The Product, f ll wing f mula: 4-n-heptylphenol, is of very low toxicity and has 03 a phenol coefficient of about 666 measured by the Reddish method now ofilcially recognized by the 50 6 2 Food, Drug and Insecticide Administration of the 50 5 3 Department of Agriculture.

4 If the amount of sulfuryl-chloride used is in- R creased, there will result a mixture of 2,6 di- 1 contemplate as within the scope of my invenchloro-4-n-heptylphenol and 2-chloro-4-ntion 4-alkylphenols having a nuclear substituent h pylphenol. If the amount of sulfuryl chloride 55 is increased to more than two molecular equivalents, that is, in the example given, is in excess of 68 g., the resulting product will be substantially all 2,6 dichloro-4-n-heptylphenol. Other chlorinating agents or chlorine itself may be used instead of sulfuryl chloride.

I have obtained 2-chloro-4-n-hexylphenol by the following method: 44 g. of 4-n-hexylphenol are mixed with 34 g. of sulfuryl chloride and after five days the material is washed with sodium bicarbonate solution and the 2-chloro-4-n-hexylphenol purified by distillation. The product is ordinarily obtained as a liquid, which is practically colorless, odorless and tasteless and boils at 275-276 C. under about 740 mm. pressure. The solid alpha naphthoate produced from this compound melts at 43-45 C. The product, 2- chloro-4-n-hexylphenol, has a phenol coeflicient of about 444, measured by the Reddish method. It has very low toxicity.

In the following table, I have given the boiling points, the melting points of the corresponding alpha-napthoates, and the phenol coefficients (determined by the Reddish method) of the various 2-chloro-4-n-alkylphenols, which I have in vestigated:

Naphtlioates Phenol coefii- M. R, a o. cient Propyl, 226227 (741 mm i 71-73 31 Butyl, 243244 (735 mm) 44-46 115 Amyl, 259-260 (740 mm) 63-65 333 Hexyl, 275-276 (740 mm) 43-45 444 Heptyl, 290-291 (738 mm) 45-47 666 In comparison with the foregoing, tests have shown that the phenol coefficients of 2-chloro-4- methylphenol and 2-chlo-ro-4-ethylphe-nol are only about 8.7 and 17.7, respectively.

' The substituted alkylphenols of my invention may be incorporated with other medicaments, or may be used dissolved in dilute alcohol, dilute alkali or other suitable solvent. Furthermore, they may be used in the form of esters, others or salts.

I am aware that the products and methods described herein may be varied considerably without departing from the spirit of my invention, and, therefore, I claim my invention broadly as indicated by the appended claims.

What I claim is: 1

1. A new product consisting of 2-chl0ro-4-nheptylphenol, said product being a practically colorless, tastless' and odorless liquid boiling at about 290 C. under a pressure of 738 mm. and having a phenol coefficient exceeding 500.

2. A new product consisting of 2-chloro-4-nhexylphenol, said product being a practically colorless, tasteless and odorless liquid, boiling at about 275 C. under a pressure of 740 mm. and having a phenol coefficient exceeding 350.

3. The process of producing a compound having a high phenol coefficient comprising subjecting 4-n-heptylphenol to reaction with sulfuryl chloride.

4. The process of producing a compound having a high phenol coeficient comprising mixing 4-n-heptylphenol and sulfuryl chloride, allowing the mixture to stand until the reaction is substantially effected and eliminating any remaining sulfuryl chloride.

5. The process of producing a compound having a high phenol coefi'lcient comprising mixing 4-n-heptylphenol with from one to three molecular equivalents of sulfuryl chloride, and allowing the mixture to stand until reaction is substantially effected.

6. The process of producing a compound having a high phenol coefiicient comprising subjecting 4-n-hexylphenol to reaction with sulfuryl chloride.

7. The process of producing a compound having a high phenol coefiicient comprising mixing 4-n-hexylphenol with from one to three molecular equivalents of sulfuryl chloride, and allowing the mixture to stand until reaction is substantially effected.

8. A 4-normal alkyl halo phenol wherein the halogen substituent occupies the ortho position with respect to the hydroxyl group and the alkyl group contains at least six carbon atoms.

9. The process of producing compounds having high phenol coefiicients comprising the treatment of a 4-normal-alkylphenol, having more than five carbon atoms in the alkyl group, with a reagent capable of introducing a halogen substituent in place of one of the hydrogen atoms.

10. The process of producing compounds having high phenol coefficients comprising the treatment of a 4-normal-alkylphenol, having more than five carbon atoms in the alkyl group, with a reagent capable of replacing one of the hydrogen atoms of the benzene ring by a halogen substituent.

11. 4-n-hexyl-2-chloro-phenol.

12. 4-n-heptyl-2-chloro-phenol.

FREDERICK F. BLICKE. 

